Microenvironment-responsive MOF nanozymes armored cryogels promoted wound healing via rapid hemostasis, infection elimination and angiogenesis

Abstract

Drug-resistant bacterial and biofilm infections, vascularization disorders, and inadequate hemostasis are the key factors that limit chronic diabetic wound healing. Here, we construct a microenvironment-responsive multifunctional platinum-armed iron-based MOF nanocomposite (Pt@FeMOF) to repair chronic wounds. Under acidic conditions (biofilm environment), Pt@FeMOF nanoparticles (NPs) produce reactive oxygen species via a synergistic Fenton reaction to eliminate both drug-resistant bacteria and their biofilms. Furthermore, based on transcriptomic results and ferroptosis marker evaluation, we reveal that the Pt@FeMOF NPs induce ferroptosis in bacteria via lipid peroxidation, GSH depletion, iron overload, and disruption of arginine metabolism. In addition, the Pt@FeMOF NPs promote vascular repair, possibly by inhibiting oxidative stress-mediated endothelial cell senescence in the microenvironment to restore angiogenesis. Finally, the Pt@FeMOF NPs are loaded into GelMA cryogels to further improve their hemostasis and exudate absorption. In vivo experiments demonstrate that Pt@FeMOF NPs-loaded cryogel dressings effectively promote MRSA- and P. aeruginosa-infected diabetic wounds. This ferroptosis-like antibacterial strategy may provide novel insights into the treatment of drug-resistant bacterial infections and fight against biofilm-associated infections. The proposed tactic provides a promising approach for the clinical treatment of diabetic wounds.